Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31727837.
- Also identified by DOI 10.1126/science.aav3487.
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Abstract
Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6-specific T helper (T<sub>H</sub>)1 and T<sub>H</sub>17 cells. However, mechanisms governing the cardiotoxicity programming of heart-specific T cells have remained elusive. Using a mouse model of spontaneous autoimmune myocarditis, we show that progression of myocarditis to lethal heart disease depends on cardiac myosin-specific T<sub>H</sub>17 cells imprinted in the intestine by a commensal <i>Bacteroides</i> species peptide mimic. Both the successful prevention of lethal disease in mice by antibiotic therapy and the significantly elevated <i>Bacteroides-</i>specific CD4<sup>+</sup> T cell and B cell responses observed in human myocarditis patients suggest that mimic peptides from commensal bacteria can promote inflammatory cardiomyopathy in genetically susceptible individuals. The ability to restrain cardiotoxic T cells through manipulation of the microbiome thereby transforms inflammatory cardiomyopathy into a targetable disease.
Medical subject headings
- Autoimmune Diseases
- Bacteroides
- Cardiomyopathy, Dilated
- Gastrointestinal Microbiome
- Myocarditis
- Peptides
- beta-Galactosidase